The overall aim of this research is to investigae the pathogenesis of Hodgkin's disease by the study of tissue cultures derived from the tumor. Cells maintained in long-term cultures have proven amendable to a variety of experimental approaches that have contributed important new information in our understanding of Hodgkin's disease. Morphologic, immunologic, and enzymatic studies indicate that monolayer cultures prepared from Hodgkin's disease splenic tumors are similar to macrophages. The cultures are capable of propagation for an indefinite period of time, have aneuploid karyotypes, and produce malignant tumors when transplanted into nude mice suggesting derivation from a malignant cell of Hodgkin's disease. Studies of circulating immune complexes in the serum of patients with Hodgkin's disease, and demonstration of the binding of such complexes to the monolayer cells indicate that the tissue cultures bear a close relation to the disorder in vivo. Based on these studies we are prepared to embark on additional experiments with 3 major objectives in mind. The first goal is to further identify and characterize cells of our Hodgkin's disease monolayer and suspension cultures. We shall perform cytogenetic studies by the giemsa-banding technique to identify specific chromosome markers and examine the cultured cells for production of biologically active factors (plasminogen activator, endogenous pyrogen, and lymphokines) and for a variety of protease and esterases. We plan to examine the interaction of Hodgkin's disease cultured cells with noncultured lymphocytes, macrophages, and granulocytes by cinemicrophotography, electron microscopy, and by a one-way mixed culture system and cytotoxicity. The second goal is to characterize biochemically the cell surface proteins of Hodgkin's disease culture cells by two dimensional electrophoresis. The third goal is to further examine the reaction of soluble immune complexes with the cultured cells, isolate complexes from the serum by sucrose gradient density sedimentation, analyze the mechanism of binding to the monolayer cells, and identify the antigenic components of the complexes.